Literature review and case study of recurrent EPGA with elevated IgG4 and positive HBsAg successfully treated with rituximab.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of autoimmune vasculitis. The involvement of IgG4 and HBsAg in EGPA is less common but can occur and may present unique challenges in management.

Case Presentation: We present a case study of a 70-year-old female diagnosed with EGPA confirmed renal biopsy.

Discovery of Potent, Specific, and Orally Available NLRP3 Inflammasome Inhibitors Based on Pyridazine Scaffolds for the Treatment of Septic Shock and Peritonitis.

The NLRP3 inflammasome is a multiprotein complex that is a component of the innate immune system, involved in the production of pro-inflammatory cytokines. Its abnormal activation is associated with many inflammatory diseases. In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors based on pyridazine scaffolds.

Altered dynamic functional connectivity of nucleus accumbens subregions in major depressive disorder: the interactive effect of childhood trauma and diagnosis.

Major depressive disorder (MDD) with childhood trauma represents a heterogeneous clinical subtype of depression. Previous research has observed alterations in the reward circuitry centered around the nucleus accumbens (NAc) in MDD patients. However, limited investigations have focused on aberrant functional connectivity (FC) within NAc subregions among MDD with childhood trauma.

Design, Synthesis, and Biological Evaluation of 5-Amino-4-fluoro-1-benzo[]imidazole-6-carboxamide Derivatives as Novel and Potential MEK/RAF Complex Inhibitors Based on the "Clamp" Strategy.

Herein, we described the rational drug design and synthesis of a series of 5-amino-4-fluoro-1-benzo[]imidazole-6-carboxamide derivatives that inhibit MEK and RAF kinases. The detailed screening cascades revealed that was a preferred compound, which might act like a "clamp" to stabilize the MEK/RAF complex, thereby effectively inhibiting MEK1, BRAF, and BRAF with IC values of 28, 3, and 3 nM, respectively. possessed an excellent selectivity over other 312 human-related kinases at 1 μM.

Spontaneous dislodgment of a peritoneal dialysis catheter inserted using the Seldinger technique: A case report.

Background: Peritoneal dialysis (PD) is an important renal replacement therapy in patients with end-stage renal disease. PD catheters remain the lifeline for patients undergoing PD. The catheter technique survival rate is considered a core PD outcome domain.

Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder.

Background: Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD.

Methods: We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma.

The molecular mechanisms of peptidyl-prolyl isomerase Pin1 and its relevance to kidney disease.

Pin1 is a member of the peptidyl-prolyl cis/trans isomerase subfamily and is widely expressed in various cell types and tissues. Alterations in Pin1 expression levels play pivotal roles in both physiological processes and multiple pathological conditions, especially in the onset and progression of kidney diseases. Herein, we present an overview of the role of Pin1 in the regulation of fibrosis, oxidative stress, and autophagy.

Effects of childhood maltreatment and major depressive disorder on functional connectivity in hippocampal subregions.

Major Depressive Disorder (MDD) with childhood maltreatment is a prevalent clinical phenotype. Prior studies have observed abnormal hippocampal activity in MDD patients, considering the hippocampus as a single nucleus. However, there is limited research investigating the static and dynamic changes in hippocampal subregion functional connectivity (FC) in MDD patients with childhood maltreatment.

Local Scaffold Diversity-Contributed Generator for Discovering Potential NLRP3 Inhibitors.

Deep generative models have become crucial tools in de novo drug design. In current models for multiobjective optimization in molecular generation, the scaffold diversity is limited when multiple constraints are introduced. To enhance scaffold diversity, we herein propose a local scaffold diversity-contributed generator (LSDC), which can be utilized to generate diverse lead compounds capable of satisfying multiple constraints.

Discovery, Optimization, and Evaluation of Potent and Selective DNA-PK Inhibitors in Combination with Chemotherapy or Radiotherapy for the Treatment of Malignancies.

Given the multifaceted biological functions of DNA-PK encompassing DNA repair pathways and beyond, coupled with the susceptibility of DNA-PK-deficient cells to DNA-damaging agents, significant strides have been made in the pursuit of clinical potential for DNA-PK inhibitors as synergistic adjuncts to chemo- or radiotherapy. Nevertheless, although substantial progress has been made with the discovery of potent inhibitors of DNA-PK, the clinical trial landscape requires even more potent and selective molecules. This necessitates further endeavors to expand the repertoire of clinically accessible DNA-PK inhibitors for the ultimate benefit of patients.

The role of the thalamic subregions in major depressive disorder with childhood maltreatment: Evidences from dynamic and static functional connectivity.

Background: Major depressive disorder (MDD) with a history of childhood maltreatment represents a highly prevalent clinical phenotype. Previous studies have demonstrated functional alterations of the thalamus among MDD. However, no study has investigated the static and dynamic changes in functional connectivity (FC) within thalamic subregions among MDD with childhood maltreatment.

Effects of childhood neglect on regional brain activity and corresponding functional connectivity in major depressive disorder and healthy people: Risk factor or resilience?

Background: Childhood neglect is a high risk factor for major depressive disorder (MDD). However, the effects of childhood neglect on regional brain activity and corresponding functional connectivity in MDD patients and healthy populations remains unclear.

Methods: Regional homogeneity, amplitude of low-frequency fluctuations (ALFF), fractional ALFF, degree centrality, and voxel-mirrored homotopic connectivity were extensively calculated to explore intraregional brain activity in MDD patients with childhood neglect and in healthy populations with childhood neglect.

Discovery and Evaluation of 3-Quinoxalin Urea Derivatives as Potent, Selective, and Orally Available ATM Inhibitors Combined with Chemotherapy for the Treatment of Cancer via Goal-Oriented Molecule Generation and Virtual Screening.

ATM plays an important role in DNA damage response and is considered a potential target in cancer therapies. In this study, a goal-directed molecular generation approach based on ligand similarity and target specificity was applied to sample active molecules, and they were screened virtually to identify the theoretical lead compound , which was later shown to inhibit ATM adequately. However, there is a main concern about its poor metabolic stability .

Data Mining and Graph Network Deep Learning for Band Gap Prediction in Crystalline Borate Materials.

Crystalline borates are an important class of functional materials with wide applications in photocatalysis and laser technologies. Obtaining their band gap values in a timely and precise manner is a great challenge in material design due to the issues of computational accuracy and cost of first-principles methods. Although machine learning (ML) techniques have shown great successes in predicting the versatile properties of materials, their practicality is often limited by the data set quality.

Podocyte Infolding Glomerulopathy: A Case Series Report and Literature Review.

Background: Podocyte infolding glomerulopathy (PIG) is a peculiar and very rare manifestation in renal pathology. Its underlying pathogenesis mechanism and clinical characteristics remain unclear due to sparse reports.

Objective: To further elucidate the clinical profile of PIG by carefully reporting our four cases and a comprehensive review of cases in the literature.

Design, synthesis and biological evaluation of purine-based derivatives as novel JAK2/BRD4(BD2) dual target inhibitors.

Based on the pharmacological synergy of JAK2 and BRD4 in the NF-κB pathway and positive therapeutic effect of combination of JAK2 and BRD4 inhibitors in treating MPN and inflammation. A series of unique 9H-purine-2,6-diamine derivatives that selectively inhibited Janus kinase 2 (JAK2) and BRD4(BD2) were designed, prepared, and evaluated for their in vitro and in vivo potency. Among them, compound 9j exhibited acceptable inhibitory activity with IC values of 13 and 22 nM for BD2 of BRD4 and JAK2, respectively.

Identifying Protein-Ligand Interactions via a Novel Distance Self-Feedback Biomolecular Interaction Network.

Efficient and accurate characterizations of protein-ligand interactions are key to understanding biology at the molecular level. They are particularly useful in pharmaceutical industry applications. They are usually computationally demanding for those widely applied dynamics-based methods in identifying important residues or calculating ligand binding free energy.

Value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission: a case report and literature review.

Backgrounds: Published literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial.

Case Presentation: Here we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis.

Lipoprotein glomerulopathy resulting from compound heterogeneous mutations of APOE gene: A case report.

Rationale: Lipoprotein glomerulopathy (LPG) is a rare glomerular disease characterized by the deposition of lipoprotein thrombi in glomerular capillaries. The disease is characterized by proteinuria, progressive renal failure, and characteristic lipoprotein thrombosis in glomerular capillaries. Rare mutations in the apolipoprotein E (APOE) gene mainly contribute to disease pathogenesis.

ANCA-associated vasculitis overlaps with systemic sclerosis: a case report and literature review.

Background: Systemic sclerosis (SSc) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) both affect the kidney and may cause renal failure. Treatment of AAV is dramatically different from that of SSc renal crisis (SRC). Kidney biopsy is not recommended for diagnosing SRC, but it is the only reliable diagnostic method for AAV.

HMGB1-TLR4-IL-23-IL-17A axis accelerates renal ischemia-reperfusion injury via the recruitment and migration of neutrophils.

Renal ischemia-reperfusion injury (IRI) is an important cause of setting off acute kidney injury. Neutrophil-mediated immunomodulation has a pivotal role in the evolving of IRI. The HMGB1-TLR4-IL-23-IL-17A axis gives rise to neutrophil activation.